Ortho-[(2,6-dichlorophenyl)amino]phenylacetic acid (hereinafter referred to as diclofenac) and its pharmaceutically acceptable salts are known compounds useful in the treatment of inflammation. Sodium [ortho[(2,6-dichlorophenyl)amino]phenyl]acetate, also variously known as 2-[2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt and diclofenac sodium, has been shown, for example, in pharmacological studies to possess potent anti-inflammatory and analgesic properties. See, for example, Riess et al., Scand. J. Rheumatol. Suppl., Vol. 22, pp. 17-29 (1978). The use of diclofenac sodium in the form of an aqueous solution in the treatment of ocular inflammation has also been shown. See, for example, M. Agata et al., Nihon Ganka Gakkai [Acta Soc. Ophthalmol. Japan], Vol. 87, pp. 19-28 (1983), and M. Agata et al., Nihon Ganka Gakkai [Acta Soc. Ophthalmol. Japan], Vol. 88, No. 6, pp. 61-66 (1984).
The transdermal delivery of diclofenac or its pharmaceutically acceptable salts has been described in various publications. For example, EP 524582 discloses a diclofenac sodium plaster. The plaster comprises a paste formulation that contains diclofenac sodium, a water-soluble polymer such as polyacrylic acid and a mixture of propylene glycol and 1-menthol as penetration enhancers.
EP 582727 discloses a transdermal therapeutic formulation that comprises a polymer having lipophilic monomer units and hydrophilic monomer units in a weight ratio of 98:2 to 0:100, a drug, an alcohol and a penetration enhancer. As suitable polymers there are mentioned acrylic adhesives such as copolymers of alkyl acrylates and acrylic acid. Among the list of alcohols there are mentioned polyols such as propylene glycol. EP 582727 further discloses that known penetration enhancers can be used such as isopropyl myristate. Diclofenac is among the list of drugs that can be used in the transdermal therapeutic formulation.
EP 452837 discloses a medical adhesive comprising a plaster layer containing the following ingredients:
(1) a medicinal ingredient; PA1 (2) a hydrophobic polymer having a glass transition temperature of -65.degree. C. to 35.degree. C.; PA1 (3) a percutaneous absorption promoting agent; PA1 (4) water, and PA1 (5) a hydrophilic polymer which is soluble or capable of swelling in water. PA1 (a) a copolymer of one or more alkyl(meth)acrylates containing 4 to 12 carbon atoms in the alkyl group and one or more hydrophilic monomers; PA1 (b) a mixture of penetration enhancers comprising: PA1 (c) a therapeutically effective amount of diclofenac or a pharmaceutically acceptable salt thereof.
The hydrophobic polymer is present in larger amounts than the hydrophilic polymer and the layer forms a water-in-oil type emulsion. It is disclosed that diclofenac can be used as the medicinal ingredient.
WO 91/09592 discloses a transdermal system with a reservoir layer that comprises a complex of the drug and a cyclo compound. The release rate of the drug from the system is controlled by the dissociation of the complex. Diclofenac is disclosed as one of the drugs that can be used in such a system.
U.S. Pat. No. 5,505,956 discloses the delivery of a drug such as diclofenac from a transdermal device that has on a backing an adhesive layer that has a laminate structure of 2 to 5 layers and each layer has different water absorption capacity. The adhesive layer contains an adhesive resin such as a polyacrylate, a penetration enhancer, a water adsorptive material such as a polyol and a lenitive agent. Pyrrolidone derivatives and higher fatty acid esters are mentioned as penetration enhancers.